A correlation method was developed to examine functional interactions between brain regions, by correlating either regional cerebral metabolic rates for glucose or regional cerebral blood flows, as determined by positron emission tomography (PET) in humans. Women had stronger functional associations than men involving left-hemisphere frontal cortices. There was a loss of frontal-parietal functional associations with age. There was a further reduction in patients with dementia of the Alzheimer type (DAT), suggesting a loss of corticocortical connections. Patients with obsessive-compulsive disorder (OCD) did not show an overall loss of functional associations, but rather a reorganization. A discriminant function involving regional interdependencies could distinguish DAT from controls. In humans in whom regional cerebral blood flow (rCBF) was measured with PET during two visual processing tasks, correlations among visual brain areaas were significant on the right side, but not the left side, suggesting a more important role for the right hemisphere. In awake Fischer-344 rats, having undergone corpus callosotomy, reduced metabolic correlations were found between left and right hemispheric brain regions, suggesting that interhemispheric interactions are mediated in part by callosal fibers. Correlations between cholinergic nuclei and frontoparietal cortex increased in rats 2 weeks after a lesion of the nucleus basalis magnocellularis. A network-simulation model was developed to partially validate the correlational analysis as applied to blood flow data, and to explore the neurobiological substrates of observed correlational patterns.